The goal of the proposed research is to examine the extent to which the action of hypolipidemic drugs can be explained on the basis of the degree of association with proteins and lipoproteins of the blood. To carry out this objective, experiments have been devised on systems of increasing complexity: drug-albumin, drug-lipoprotein; drug-albumin-lipoprotein; and finally, on a reconstituted system of drug-lipoprotein-albumin-cells. A comparison of clofibrate, halofenate, nafenopin, and RMl 14,514, which differ in the proportion of aliphatic chains and in relative biological potencies is basic towards the resolution of the proposed mechanism. The data generated, namely equilibrium association constants, free energy of binding, extent of electrostatic and hydrophobic interactions, and drug transport by mitochondria or cells; the analytical approach of equilibrium dialysis, gas liquid chromatography for the resolution of low concentrations of drugs and drug mixtures; all provide information on aspects of drug-lipoprotein interaction, and are therefore valuable to understand the pharmacological properties of this group of drugs.